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Moderate Vs. Mild Cases of Overseas-Imported COVID www.nature.com/scientificreports OPEN Moderate vs. mild cases of overseas‑imported COVID‑19 in Beijing: a retrospective cohort study Wenliang Zhai1,13, Zujin Luo2,13, Yue Zheng3,13, Dawei Dong4,13, Endong Wu5, Zhengfang Wang6, Junpeng Zhai7, Yujuan Han8, Huan Liu9, Yanran Wang10, Yaohui Feng11, Jing Wang1* & Yingmin Ma12* This study compared the diferences in the clinical manifestations, treatment courses and clinical turnover between mild and moderate coronavirus disease 2019 (COVID‑19). Clinical data of the patients with imported COVID‑19 admitted to Beijing Xiaotangshan Designated Hospital between March 15 and April 30, 2020, were retrospectively analysed. A total of 53 COVID‑19 patients were included, with 21 mild and 32 moderate cases. Compared with the mild group, the moderate group showed signifcant diferences in breathing frequency, lymphocyte count, neutrophil percentage, neutrophil/lymphocyte ratio, procalcitonin, C‑reactive protein, and dynamic erythrocyte sedimentation rate. In the moderate group, 87.5% exhibited ground‑glass opacities, 14% exhibited consolidative opacities, 53.1% exhibited local lesions and 68.8% exhibited unilateral lesions. The proportion of patients who received antiviral or antibiotic treatment in the moderate group was higher than that in the mild group, and the number of cases that progressed to severe disease in the moderate group was also signifcantly higher (18.7% vs. 0%, p = 0.035). Compared with patients with mild COVID‑19, those with moderate COVID‑19 exhibited more noticeable infammatory reactions, more severe pulmonary imaging manifestations and earlier expression of protective antibodies. The overall turnover of the moderate cases was poorer than that of the mild cases. Population mobility between countries as well as between regions exacerbates the spread of COVID-19, resulting in unprecedented pressure from imported cases1. By 24:00 on June 2, 2020, a total of 1,762 overseas-imported cases had been reported in China, which were distributed in 28 provinces and cities in the country2. COVID-19 has become a global health emergency that seriously threatens human health. Clinical manifestations of COVID-19 vary greatly, from the absence of symptoms to severe dyspnoea or even death. Old age, obesity, diabetes complications, hypertension, coronary artery disease and tumours are risk fac- tors for COVID-19 aggravation and related death 3,4. Populations with these characteristics have received great attention from scholars and clinicians. However, all populations are susceptible to SARS-CoV-2, and the number 1Department of Emergency, Xuanwu Hospital, Capital Medical University, No.45 Changchunjie Street, Xicheng District, Beijing 100053, China. 2Department of Respiratory and Critical Care Medicine, Beijing Engineering Research Center of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing 100043, China. 3Department of Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. 4Department of Radiology, Beijing Xiaotangshan Hospital, Beijing 102211, China. 5Department of Critical Medicine, Beijing Chest Hospital, Beijing 101149, China. 6Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. 7Department of Endocrinology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. 8General Internal Medicine, Beijing Xiaotangshan Hospital, Beijing 102211, China. 9Department of Health Education, Beijing Xiaotangshan Hospital, Beijing 102211, China. 10Department of Nephrology, Hospital of Capital Institute of Pediatrics, Beijing 100020, China. 11Department of Geriatrics, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China. 12Beijing Youan Hospital, Capital Medical University, Beijing 100069, China. 13These authors contributed equally: Wenliang Zhai, Zujin Luo, Yue Zheng and Dawei Dong. *email: [email protected]; [email protected] Scientifc Reports | (2021) 11:6483 | https://doi.org/10.1038/s41598-021-85869-0 1 Vol.:(0123456789) www.nature.com/scientificreports/ of non-severe patients is enormous 5, which accounts for approximately 81% of the total number of COVID- 19 patients. Tese non-severe patients are likely to be ignored due to milder symptoms, fewer complications, stronger body tolerance and fewer medical demands. Moreover, reports on the clinical characteristics, disease classifcation and disease turnover of these patients are relatively rare 6,7. Due to the complexity of COVID-19, experts have suggested classifying COVID-19 infection into mild, moderate, severe and critically severe types based on the clinical manifestations, CT imaging and laboratory outcomes of the patients8,9. As neither the mild type nor the moderate type belongs to an emergent condition, observational and treatment protocols for these patients are basically the same. Although CT imaging is able to diferentiate between these two types, the selection of treatment protocols for these two types seems to have no direct relation with the classifcation outcomes. Whether it is necessary to diferentiate patients with mild COVID-19 from those moderate disease according to CT images remains clinically complex. Confronted with such complexity, as well as a lack of sufcient research on patients with non-severe COVID- 19, we retrospectively analysed the clinical characteristics on admission, disease progression during treatment and clinical outcomes of patients with mild and moderate overseas-imported COVID-19, and the necessity of the diferentiation between mild COVID-19 and moderate COVID-19 was also discussed. Results Clinical manifestations. A total of 2171 suspected patients were screened, and 53 were fnally confrmed with COVID-19 and hospitalized (2117 with a negative result and one with severe COVID-19 were excluded according to nucleic acid detection) (Fig. 1). Te baseline data of the included patients are summarized in Table 1. All patients were imported from overseas, and 52.4% of the mild group and 46.9% of the moderate group were from the UK (P = 0.695), with the rest from France, America, Serbia, Spain and Tailand. Te mild group and the moderate group had no signifcant diferences in age, sex ratio, history of contact with confrmed or suspected COVID-19 patients, complications, or history of smoking. Fever, pharyngalgia or dry pharynx and tussiculation were the most common symptoms among the included patients. Te moderate group showed a signifcantly higher breathing frequency in the resting state on admission than the mild group (18.0 [17.0–20.0] vs. 18.0 [18.0–19.0], P = 0.042). Laboratory and imaging examination. Te count and percentage of lymphocytes in the moderate group were signifcantly lower than those in the mild group (P = 0.010 and P = 0.003, respectively; Table 2). Te neutrophil percentage of the moderate group was signifcantly higher than that of the mild group (P < 0.001), whereas no signifcant diference in the neutrophil count was observed (P = 0.068). Te NLR of the moderate group was signifcantly higher than that of the mild group (P < 0.001). Compared with the mild group, the mod- erate group also exhibited higher levels of ALT, creatinine, fbrinogen, PCT, CRP and ESR but a lower HDL level. In the moderate group, 28 patients (87.5%) exhibited GGO, 14 (43.8%) exhibited consolidation, 17 (53.1%) exhibited local lesions and 22 (68.8%) exhibited unilateral lesions. Figure 2 shows some typical examples of the CT images. Te median CT score of the moderate group was 2 1–3. In contrast, the mild group did not exhibit characteristic changes according to the CT images. Treatment and outcomes. Te proportion of patients who received chloroquine or arbidol antiviral treat- ment in the moderate group was higher than that in the mild group (Table 3). In the moderate group, 12 patients (37.5%) received oral administration of moxifoxacin or cefaclor for bacterial infection, whereas in the mild group, no patients received antibiotic treatment. Antibody detection at a 3-d interval showed earlier positive expression of IgG in the moderate group than in the mild group (P = 0.014). No characteristic emergence of positive IgM was detected (41 patients (77.3%) were not detected with positive IgM even by 28 d afer discharge). During hospitalization, 6 patients in the moderate group exhibited aggravated pneumonia, which met the diag- nostic criterion for severe pneumonia. Tese patients were subjected to intranasal oxygen inhalation and then transferred to other centres for further treatment. Among the 6 patients, 2 needed mechanical ventilation afer the emergence of ARDS (Fig. 3), and 2 patients exhibited secondary infections, with one presenting with her- pangina and the other complicated with infuenza virus type A. Except for the 6 severe patients, all patients in the two groups were cured and discharged. Te two groups did not show signifcant diferences in the time span from disease onset to symptom improvement or the hospital stay. No sequelae were observed in the two groups at the time of discharge or at 28 d afer discharge. Additionally, no signifcant diference in hospitalization costs was observed between the two groups (P > 0.05). Intra‑moderate group comparison. In this study, 6 patients with moderate COVID-19 exhibited disease aggravation during treatment, and they were compared with the remaining patients in the same group (n = 26). Te results are summarized in Table 4. Tese patients presented with a lower lymphocyte count than the patients whose prognoses were better (1.13 [0.82–1.72] vs. 1.86 [1.34–2.55]; p = 0.033). Among the 6 patients, 3 had lymphopenia, and 2 had lymphocyte counts near the lower threshold of the normal reference range at the time of admission. In addition, they pre- sented with signifcantly higher NLR (2.82 [1.68–4.77] vs. 1.62 [1.15–2.06]; p = 0.049), CRP (20.92 [15.04–52.20] vs. 1.47 [0.27–4.13]; p = 0.002) and LDH (206.6 [181.7–300.4] vs. 175.7 [143.9–201.8]; p = 0.041). Discussion COVID-19 patients exhibit varied symptoms.
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